Rebecca N Jerome

A Systematic Review of Medical Treatments for Children With Autism Spectrum Disorders

CONTEXT: As many as 1 in every 110 children in the United States has an autism spectrum disorder (ASD). Many medical treatments for ASDs have been proposed and studied, but there is currently no consensus regarding which interventions are most effective. OBJECTIVE: To systematically review evidence regarding medical treatments for children aged 12 years and younger with ASDs. METHODS: We searched the Medline, PsycInfo, and ERIC (Education Resources Information Center) databases from 2000 to May 2010, regulatory data for approved medications, and reference lists of included articles. Two reviewers independently assessed each study against predetermined inclusion/exclusion criteria. Studies of secretin were not included in this review. Two reviewers independently extracted data regarding participant and intervention characteristics, assessment techniques, and outcomes and assigned overall quality and strength-of-evidence ratings on the basis of predetermined criteria. RESULTS: Evidence supports the benefit of risperidone and aripiprazole for challenging and repetitive behaviors in children with ASDs. Evidence also supports significant adverse effects of these medications. Insufficient strength of evidence is present to evaluate the benefits or adverse effects for any other medical treatments for ASDs, including serotonin-reuptake inhibitors and stimulant medications. CONCLUSIONS: Although many children with ASDs are currently treated with medical interventions, strikingly little evidence exists to support benefit for most treatments. Risperidone and aripiprazole have shown benefit for challenging and repetitive behaviors, but associated adverse effects limit their use to patients with severe impairment or risk of injury.

Evolution of a Mature Clinical Informationist Model

Achieving evidence-based practice will require new approaches to providing information during health care delivery and to integrating evidence and informatics at the point of care. To support evidence-based practice, Vanderbilt University Medical Centers Eskind Biomedical Library (EBL) introduced the role of clinical informationist, an information specialist with sufficient knowledge and insight to function as a true partner in the health care team. To further disseminate evidence-based knowledge, the Vanderbilt University Medical Centers (VUMC) electronic medical record system and pathway development processes integrate advanced information synthesis capabilities provided by clinical informationists. Combining clinical informationist expertise with informatics tools is an effective strategy for delivering the evidence needed to support patient care decisions.

Progestogens for Preterm Birth Prevention A Systematic Review and Meta-Analysis

OBJECTIVE: We systematically reviewed the effectiveness of progestogens for prevention of preterm birth among women with prior spontaneous preterm birth, multiple gestations, preterm labor, short cervix, or other indications. DATA SOURCES: We searched MEDLINE and EMBASE databases for English language articles published from January 1966 to October 2011. METHODS OF STUDY SELECTION: We excluded publications that were not randomized controlled trials or had fewer than 20 participants, identifying 34 publications, of which 19 contained data for Bayesian meta-analysis. TABULATION, INTEGRATION, AND RESULTS: Two reviewers independently extracted data and assigned overall quality ratings based on predetermined criteria. Among women with prior preterm birth and a singleton pregnancy (five randomized controlled trials), progestogen treatment decreased the median risk of preterm birth by 22% (relative risk [RR] 0.78, 95% Bayesian credible interval 0.68–0.88) and neonatal death by 42% (RR 0.58, 95% Bayesian credible interval 0.27–0.98). The evidence suggests progestogen treatment does not prevent prematurity (RR 1.02, 95% Bayesian credible interval 0.87–1.17) or neonatal death (RR 1.44, 95% Bayesian credible interval 0.46–3.18) in multiple gestations. Limited evidence suggests progestogen treatment may prevent prematurity in women with preterm labor (RR 0.62, 95% Bayesian credible interval 0.47–0.79) and short cervix (RR 0.52, 95% Bayesian credible interval 0.36–0.70). Across indications, evidence about maternal, fetal, or neonatal health outcomes, other than reducing preterm birth and neonatal mortality, is inconsistent, insufficient, or absent. CONCLUSION: Progestogens prevent preterm birth when used in singleton pregnancies for women with a prior preterm birth. In contrast, evidence suggests lack of effectiveness for multiple gestations. Evidence supporting all other uses is insufficient to guide clinical care. Overall, clinicians and patients lack longer-term information to understand whether intervention has the ultimately desired outcome of preventing morbidity and promoting normal childhood development.

Providing Evidence-Based Answers to Complex Clinical Questions: Evaluating the Consistency of Article Selection

Purpose Health care providers must maintain familiarity with current biomedical evidence, but clinicians struggle to maintain their awareness of current research because of the demands of daily practice and the exponential growth of medical knowledge. Clinical information specialists (informationists), trained experts in reviewing and filtering the medical literature in response to complex clinical queries, may be able to assist practicing clinicians. This study compared informationists and two categories of physicians in their article selection in response to two complex clinical questions. Method The study was performed at Vanderbilt University Medical Center. A total of 15 faculty and staff from three groups were recruited (five general physicians, five physicians trained in research methodology, and five informationists). The participants reviewed two previously selected clinical questions, worked in focus groups to define the pertinent facet questions of the questions, and then ranked the articles by pertinence to the clinical questions. Results In general, both informationists and physicians trained in research methodology had a high degree of intergroup agreement for ranking article pertinence, while the generalists were less likely to agree on pertinent articles. Conclusions These findings suggest that informationists consistently select articles relevant to answering complex clinical queries and may assist practicing clinicians by providing information relevant to patient cases.

Genetic epidemiology of pelvic organ prolapse: a systematic review

Given current evidence supporting a genetic predisposition for pelvic organ prolapse, we conducted a systematic review of published literature on the genetic epidemiology of pelvic organ prolapse. Inclusion criteria were linkage studies, candidate gene association and genome-wide association studies in adult women published in English and indexed in PubMed through Dec. 2012, with no limit on date of publication. Methodology adhered to the PRISMA guidelines. Data were systematically extracted by 2 reviewers and graded by the Venice criteria for studies of genetic associations. A metaanalysis was performed on all single nucleotide polymorphisms evaluated by 2 or more studies with similar methodology. The metaanalysis suggests that collagen type 3 alpha 1 (COL3A1) rs1800255 genotype AA is associated with pelvic organ prolapse (odds ratio, 4.79; 95% confidence interval, 1.91-11.98; P = .001) compared with the reference genotype GG in populations of Asian and Dutch women. There was little evidence of heterogeneity for rs1800255 (P value for heterogeneity = .94; proportion of variance because of heterogeneity, I(2) = 0.00%). There was insufficient evidence to determine whether other single nucleotide polymorphisms evaluated by 2 or more papers were associated with pelvic organ prolapse. An association with pelvic organ prolapse was seen in individual studies for estrogen receptor alpha (ER-α) rs2228480 GA, COL3A1 exon 31, chromosome 9q21 (heterogeneity logarithm of the odds score 3.41) as well as 6 single nucleotide polymorphisms identified by a genome-wide association study. Overall, individual studies were of small sample size and often of poor quality. Future studies would benefit from more rigorous study design as outlined in the Venice recommendations.

Organ preservation in a brain dead patient: information support for neurocritical care protocol development.

In response to a traumatic brain injury or another tremendous physiologic ‘‘insult’’ to the brain (e.g., hemorrhagic or ischemic stroke), some patients suffer global and irreversible loss of brain stem function, leading to a diagnosis of brain death. Some of these patients may be candidates for organ and tissue donation, a decision mediated by the patient’s previously expressed wishes, sometimes in the form of an advance directive or organ donor card, and the preferences of the patient’s family [1]. Organ donation is truly a family-driven process and can be affected by various social, educational, and spiritual considerations. An organ procurement organization (OPO) representative or specially trained hospital staff member is typically responsible for communicating with family members about the process of organ donor management and the ways tissue and organ donation will benefit other patients in need. Because significant emotional issues may be involved with the loss of a loved one, educating the family and sincere sensitivity regarding their needs and wishes are crucial to the organ donation process. Organ donation also includes a complex set of medical practices. Key steps in beginning the process involve diagnosing and managing the brain dead patient, referred to in the literature as the brain dead cadaver and clinically defined as a patient who is comatose and shows no evidence of brain stem reflexes (e.g., spontaneous breathing, further defined in Table 1). These are important issues, given the ever-increasing demand for viable organs and list of individuals waiting for transplants. According to the US Organ Procurement and Tissue Transplantation Network in January 2007, nearly 100,000 people were waiting for organ transplants, with only approximately 26,000 patients receiving transplants between November 2006 and January 2007 [2]. A major issue in a hospital’s neurocritical care unit (NCU) setting is management of the brain dead cadaver, with a focus on optimizing the preservation of donor organs and the transfer of those organs to transplant candidates in other care facilities. Managing the organ donor following determination of brain death is multifaceted and involves a comprehensive system for medical care of the donor, which may include administering appropriate medications to maintain basic body and organ functions and monitoring physiologic values like oxygen, hormone, and electrolyte levels in the blood. Proper management of the organ donor is extremely important to ensure that organs are preserved and protected prior to harvesting and to optimize the number and quality of organs and tissues available for transplantation. Organ preservation prior to withdrawal of extraordinary means of support (e.g., pharmacologic support of hemodynamics, ventilator support of respiration) involves both monitoring and maintaining physiologic values within set parameters to avoid damage and maintain organ function. These parameters include blood pressure, respiratory rate, and fluid and electrolyte status. Function and levels can be maintained through administration of medications such as corticosteroids and thyroid hormones, as well as through adjustments to ventilator settings and fluid administration to maintain respiratory rate and electrolyte balance. Synchronous management of the brain dead cadaver, the patient’s family, and the members of the clinical team is crucial to ensure functioning of the implanted organ once it is transplanted. Transferring the organ from donor to recipient should be executed as quickly as possible. The wishes of family members and the actions of the care team and of the OPO representatives are important elements in managing the treatment course and process outcomes.

Phenotype-Driven Plasma Biobanking Strategies and Methods

Biobank development and integration with clinical data from electronic medical record (EMR) databases have enabled recent strides in genomic research and personalized medicine. BioVU, Vanderbilt’s DNA biorepository linked to de-identified clinical EMRs, has proven fruitful in its capacity to extensively appeal to numerous areas of biomedical and clinical research, supporting the discovery of genotype-phenotype interactions. Expanding on experiences in BioVU creation and development, we have recently embarked on a parallel effort to collect plasma in addition to DNA from blood specimens leftover after routine clinical testing at Vanderbilt. This initiative offers expanded utility of BioVU by combining proteomic and metabolomic approaches with genomics and/or clinical outcomes, widening the breadth for potential research and subsequent future impact on clinical care. Here, we describe the considerations and components involved in implementing a plasma biobank program from a feasibility assessment through pilot sample collection.

Addressing Hemolysis in an Infant Due to Mother–Infant ABO Blood Incompatibility

This issue of the Journal of the Medical Library Association (JMLA) honors the life of and contributions to medical librarianship of Estelle Brodman, PhD. Dr. Brodmans interests in medical bibliography, automation, international collaboration, education, the history of medicine, and the profession were far reaching, and her ideas reflected innovation and a strong desire to grow the profession and skills of medical librarians [1, 2]. Since that time, medical librarianship has continued to evolve, realizing many of the ideas Dr. Brodman and others advocated. For example, the availability of medical databases and widespread use of computers in libraries have improved library processes and the ability to quickly locate information. With her strong advocacy of lifelong learning, Dr. Brodman also serves as an important role model as a librarian/educator, and she would likely have been pleased to see the professions emphasis on continuing education and research [3, 4]. As McClure noted in her discussion of Dr. Brodman as a historian, Dr. Brodman found that the study of history “often illuminates the meaning of the present and indicates logical possibilities for the future” [5]. The history of the development of neonatal critical care, like that of medical librarianship, has doubtless been influenced and evolved by pioneering thinkers. One such thinker and contemporary of Dr. Brodman, Mildred T. Stahlman, MD, was also a leader in education, practice, and research in her chosen field, neonatal critical care medicine. In 1961, Dr. Stahlman, known as the pioneer of modern neonatal intensive care, led a National Institutes of Health research project to explore the physiological aspects of the developing fetus and changes that occur at birth [6, 7]. At a critical point in her research, Dr. Stahlman made the groundbreaking decision to adapt a scaled-down respirator, a breathing machine originally developed for polio patients, to assist breathing in an infant born with severe hyaline membrane disease, a lung disease seen in premature infants whose lungs have not yet fully developed. The infant, who previously faced certain death, was able to survive with this first-ever respiratory therapy that gave a viable treatment option for preterm babies with underdeveloped lungs [6, 8]. This groundbreaking research led Dr. Stahlman to develop the first modern neonatal intensive care unit (NICU) at Vanderbilt University Medical Center [6]. Today, NICUs have become an essential part of health care in the United States for critically ill infants and their families, providing constant observation and care for these babies. Premature babies, infants born earlier than thirty-seven weeks gestation (the typical threshold for defining normal gestation) [9], represent a high percentage of those cared for by a NICU. These babies often have a variety of developmental issues requiring intensive treatment. Given the constantly evolving state of clinical research, NICU teams frequently encounter information needs requiring consultation of the medical literature.

The impact of a literature consult service on geriatric clinical care and training in falls prevention

The importance of developing effective health care programs and services for elderly persons in the United States is increasing at warp speed due to significant projected growth in the size of this demographic in the near future. According to the US Census Bureau, the number of persons aged 65 years and older is expected to rise from an estimated 35 million people in 2000 to 55 million by the year 2020 [1]. The rapid growth in this age group can be explained in part by a considerable rise in the number of older people projected for 2011, when the Baby Boom generation (persons born between 1946 and 1964) begins to turn 65 years old. The number of oldest old (persons aged 85 years and older) is projected to double from 4.7 million in 2003 to 9.6 million by 2030 [2]. The growth is also partly explained by a steady increase in life expectancy from birth for both men and women, regardless of ethnicity, over the last century, currently at an all-time high of 77.9 years [3], compared to 49.2 years in 1900 [4]. Providing appropriate health care services for this age group is also gaining prominence in the United States [5, 6]. Geriatrics is the branch of medicine that focuses on prevention, diagnosis, and treatment of diseases in the aged and on the socioeconomic matters that affect health care services for elderly persons. Geriatrics research and clinical practice encompass both persons residing with or without caregivers at home and those receiving clinical care at hospitals and nursing facilities [7]. In addition to managing the care of aged patients, the key goals of geriatric medicine include training medical students, physicians, and other health care professionals in geriatric issues as well as researching the aging process and the accompanying conditions affecting the elderly [8]. One of the major issues targeted by geriatric medicine is the prevention of accidental falls [9]. Falls are a common health risk, can occur in virtually any setting, and can be fatal, particularly among individuals sixty-five years and older [10]. Complications due to falls are the leading cause of death due to injury in this age group in the United States. Falls are also one of the primary causes prompting emergency care and hospitalizations among the elderly [10]. These disturbing statistics have brought this issue under significant scrutiny by geriatric clinicians and researchers in medicine.

Motivation for Launching a Cancer Metastasis Inhibition (CMI) Program

Metastatic cancers impose significant burdens on patients, affecting quality of life, morbidity, and mortality. Even during remission, microscopic metastases can lurk, but few therapies directly target tumor cell metastasis. Agents that interfere with this process would represent a new paradigm in cancer management, changing the ‘waiting game’ into a time of active prevention. These therapies could take multiple forms based on the pathways involved in the metastatic process. For example, a phenome-wide association study showed that a single nucleotide polymorphism in the gene TBXA2R is associated with increased metastasis in multiple primary cancers (P = 0.003), suggesting clinical applicability of TBXA2R antagonists. Emerging data related to the role of platelets in metastasis are concordant with our sense that these pathways present significant opportunities for therapeutic development. However, before real progress can be made toward clinical targeting of the metastatic process, foundational work is needed to define informative measures of critical elements such as circulating tumor cells and tumor DNA, and circulatory vs. lymphatic spread. These challenges require an expansion of team science and composition to obtain competitive funding. At our academic medical center, we have implemented a Cancer Metastasis Inhibition (CMI) program investigating this approach across multiple cancers.